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S. J. Heflin, C. W. Yee, K. A. Vessey, G. L. Yarbrough, R. G. Gregg, M. A. McCall; Spontaneous and Visually Evoked Responses of Retinal Ganglion Cells Between nob and nob/nob4 Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3848. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Nycnob (nob) and Grm6nob4 (nob4) mice harbor mutations in elements of the mGluR6 signaling cascade in depolarizing bipolar cells (DBCs). Although both mutants have a similar ERG phenotype (normal a-wave, negative b-wave), spontaneous and visually evoked responses of their retinal ganglion cells (RGCs) differ. Many nob RGCs burst regularly and spontaneously, whereas nob4 RGCs are similar to C57l/B6J (WT) and lack a bursting component in their spontaneous activity (SA). nob4 OFF RGCs have center/surround receptive field (RF) organization, although nob4 ON RGCs are abnormal. Both OFF and ON nob RGCs have abnormal RF organization. We hypothesized that if nyctalopin and mGluR6 function within the same mGluR6 cascade, the downstream RGC phenotype would prevail. Alternatively, the proteins could function in different aspects of the cascade and RGC phenotype in double mutants would differ from the parental phenotypes.
We created nob/nob4 double mutants and compared their SA and visually evoked responses in vivo to WT and nob RGCs. In vivo responses were evoked at light and dark adapted levels, using full field stimuli (stimulus intensity 0 to 3, or 150 cd/m2). Intracellular whole cell patch clamp recordings characterized SA in age-matched RGCs in vitro. Bursting activity was characterized using Fast Fourier Transformations (FFT) and visually evoked responses were characterized from averaged responses.
All nob RGCs had similar SA levels, unlike WT where SA was significantly higher in ON than OFF RGCs. nob/nob4 RGCs tended to have lower SA than either WT ON or nob RGCs. WT RGCs did not burst in vivo or in vitro. In contrast, the SA of 50% of nob RGCs bursting with a fundamental (F1) frequency between 3 and 5 Hz. The SA of nob/nob4 RGCs also burst, and had a significant F1 component whose range overlapped nob RGCs. Unlike WT, significantly more nob and nob/nob4 RGCs lacked a visual response and a defined RF. Both nob and nob/nob4 RGCs required bright full field stimuli to elicit a response.
Visual response properties of nob/nob4 RGCs are most similar to nob RGCs. If a difference occurs it is in the bursting characteristics of the SA. The results are most consistent with the notion that nyctalopin and mGluR6 are parts of a linear transduction cascade. Because of the significant changes in the visually evoked responses in both nob and nob/nob4 RGCs, the data support the idea that the ON pathway, via DBCs, interacts with the OFF pathway and shapes the responses of OFF-center RGCs.
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